Do Residents Believe that Onchocerciasis Transmission Was Eliminated? Results of A Post-Treatment Surveillance Knowledge, Attitude, and Practices Survey in Three Foci of Uganda.

In Uganda, 15 of 17 foci have interrupted transmission of onchocerciasis (river blindness) and stopped mass drug administration (MDA) of ivermectin. This 2016 study describes the results of a knowledge, attitude, and practices survey regarding river blindness among participants (N = 1,577) 3-5 years after ivermectin MDA was halted in three foci: Imaramagambo halted in 2012, Kashoya-Kitomi in 2013, and Mt. Elgon in 2011. The study showed high levels of composite knowledge (focus-specific range: 66.8-81.2%) related to river blindness transmission, signs, symptoms, and treatment. However, 38.1% of respondents did not know that blackflies transmitted river blindness. Notably, 72.2% claimed they had not been informed why MDA was stopped, 56.3% did not believe river blindness had been eliminated, and 83.1% wanted ivermectin MDA to resume. During the 3-5 year post-treatment surveillance period, only 27.7% (438 of 1,577) reported being informed of what to do once treatments stopped, with the most knowledgeable hailing from the Mt. Elgon focus (47.9%). This study reinforces the need for programs to intensify health education and information dissemination when MDA is stopped. Programs must remind residents that although biting insects may persist, they no longer transmit river blindness. Incorporating messages about the elimination of river blindness into community health education campaigns can help improve the community's perceptions related to the disease's absence and the ending of a long-standing MDA intervention.

Integrated Prevalence Assessment of Wuchereria bancrofti and Onchocerca volvulus in Three Co-Endemic Districts of Gambella Region, Ethiopia.

Lymphatic filariasis (LF) and onchocerciasis (OV) are among the neglected tropical diseases (NTD) targeted for elimination in Ethiopia. We used a transmission assessment survey (TAS-1) to evaluate the serological status of OV in three co-endemic districts in Gambella simultaneously. During May and June 2019, blood samples were collected from 6- to 7-year-old children who were randomly selected through standard community-based TAS methodology. Children were tested for both circulating filarial antigen (CFA) for LF via filariasis test strip and for Onchocerca volvulus 16 (Ov16) antibody for OV via laboratory-based ELISA. A total of 3,377 children from 150 villages in the three districts were tested; 1,823 (54.0%) were male. All three districts had CFA results below the critical threshold for stopping LF mass drug administration (MDA). In contrast, 40 children (1.2%) were positive for Ov16 antibody, well above the WHO's OV stop MDA threshold of 0.1%. The integrated assessment indicated two programmatic decisions: stop MDA for LF and continue MDA for OV. Accordingly, albendazole MDA was discontinued in the districts but ivermectin MDA continued. This integrated assessment showed that a random sample for TAS can give important information about OV transmission status in co-endemic areas.

Elimination of Simulium neavei-Transmitted Onchocerciasis in Wambabya-Rwamarongo Focus of Western Uganda.

Wambabya-Rwamarongo onchocerciasis focus is one of the eight foci Uganda verified using the WHO verification guidelines. The approach for elimination was twice yearly treatment with ivermectin for every round, treating at least 90% of all the eligible population. This was in combination with vector elimination using Abate® (BASF SE, Limburgerhof, Germany) since elimination nationwide policy was launched. From 2008 to 2013, the program distributed ivermectin with a mean treatment coverage of the ultimate treatment goal (UTG) or eligible population of 91.2%, with a range of 85-96%. In 2009, vector elimination based on ground larviciding had a dramatic impact on the Simulium vectors, as the last fly was observed in October 2009. No more Simulium vectors were observed during a period of at least 7 years, including the 3-year posttreatment surveillance (PTS) until the focus was reclassified as eliminated in August 2017. During the PTS period, none of the 10,578 trapped crabs were found infested with the aquatic stages of the vector. The last infested crab was observed in March 2010, and for at least 7 years, no infested crabs were observed. Serological surveys showed that of 2,978 young children examined in 2013, only one was OV16 positive (0.0%; 95% CI: 0-0.21). In 2017, after the PTS period, all 3,079 young children examined were negative for OV16 (95% CI: 0-0.16). Therefore, entomological and serological results provided evidence that resulted in the reclassification of Wambabya-Rwamarongo focus from "transmission interrupted" to "transmission eliminated" with no possibility of recrudescence.

Historical Elimination of Onchocerciasis from Victoria Nile Focus in Central Uganda Verified Using WHO Criteria.

Uganda has verified elimination of seven onchocerciasis foci since 2007 when the nationwide onchocerciasis elimination policy was launched. However, the Victoria Nile focus (which was eliminated in the early 1970s) had not been verified. The objective of this study was to verify this focus to the WHO verification guidelines and bring it in line with recently eliminated foci. Vector control with dichlorodiphenyltrichloroethane was the main intervention used at the Victoria Nile from the 1950s to the 1970s. Historical fly collection sites along River Nile were identified for recent fly collection. Relevant health workers near the sites were trained to supervise fly collection activity. With support from communities, fly collectors were identified, trained, and equipped to collect Simulium flies for at least a year. A total of 854 Simulium flies were collected and analyzed by polymerase chain reaction to detect Onchocerca volvulus DNA. The communities and their leaders provided consent for the collection of dry blood spots (DBS) from children younger than 10 years for investigation of recent exposure to the disease. A total of 2,953 DBS were collected and analyzed by OV16 ELISA to detect the presence of IgG4 antibodies recognizing the OV16 antigen. The results showed that none of the flies carried O. volvulus DNA. Similarly, all the children were OV16 negative, showing no exposure to onchocerciasis. All the flies collected were identified as Simulium adersi, which is not a known vector for O. volvulus. The results confirmed that onchocerciasis and its vector Simulium damnosum had been eliminated in the Victoria Nile focus.

Data-driven modelling and spatial complexity supports heterogeneity-based integrative management for eliminating Simulium neavei-transmitted river blindness.

Concern is emerging regarding the challenges posed by spatial complexity for modelling and managing the area-wide elimination of parasitic infections. While this has led to calls for applying heterogeneity-based approaches for addressing this complexity, questions related to spatial scale, the discovery of locally-relevant models, and its interaction with options for interrupting parasite transmission remain to be resolved. We used a data-driven modelling framework applied to infection data gathered from different monitoring sites to investigate these questions in the context of understanding the transmission dynamics and efforts to eliminate Simulium neavei- transmitted onchocerciasis, a macroparasitic disease that causes river blindness in Western Uganda and other regions of Africa. We demonstrate that our Bayesian-based data-model assimilation technique is able to discover onchocerciasis models that reflect local transmission conditions reliably. Key management variables such as infection breakpoints and required durations of drug interventions for achieving elimination varied spatially due to site-specific parameter constraining; however, this spatial effect was found to operate at the larger focus level, although intriguingly including vector control overcame this variability. These results show that data-driven modelling based on spatial datasets and model-data fusing methodologies will be critical to identifying both the scale-dependent models and heterogeneity-based options required for supporting the successful elimination of S. neavei-borne onchocerciasis.

The Galabat-Metema cross-border onchocerciasis focus: The first coordinated interruption of onchocerciasis transmission in Africa.

BACKGROUND: Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented. METHODS/PRINCIPLE FINDINGS: The Galabat-Metema focus involves neighboring districts on the border between Sudan and Ethiopia. Mass drug administration (MDA) was provided once and subsequently twice per year in this focus, with twice-per-year beginning in Ethiopia's Metema subfocus in 2016 and in the Sudan's Galabat subfocus in 2008. Ov16 ELISA-based serosurveys were conducted in 6072 children under 10 years of age in the Metema subfocus in 2014, and 3931 in the Galabat in 2015. Between 2014 and 2016, a total of 27,583 vector Simulium damnosum flies from Metema and 9,148 flies from Galabat were tested by pool screen PCR for Onchocerca volvulus O-150 DNA. Only 8 children were Ov16 seropositive (all in the Metema subfocus); all were negative by skin snip PCR. The upper limit of the 95% confidence interval (UCL) for Ov16 seropositive was <0.1% for the overall focus and 0.14 positive fly heads per 2000 (UCL = 0.39/2000). However, an entomological 'hotspot' was detected on the Wudi Gemzu river in Metema district. The hotspot was confirmed when 4 more positive fly pools were found on repeat testing in 2017 (1.04 L3/2000 flies (UCL = 2.26/2000). Information exchange between the two countries led to stopping MDA in a coordinated fashion in 2018, with the exception of the hotspot at Wudi Gemzu, where MDA with ivermectin was increased to every three months to hasten interruption of transmission. CONCLUSION: Coordinated stop MDA decisions were made by Sudan and Ethiopia based on data satisfying the World Health Organization's criteria for interruption of onchocerciasis transmission. Definitions of entomological 'hotspots' and buffer zones around the focus are proposed.

Accelerating river blindness elimination by supplementing MDA with a vegetation "slash and clear" vector control strategy: a data-driven modeling analysis.

Attention is increasingly focusing on how best to accelerate progress toward meeting the WHO's 2030 goals for neglected tropical diseases (NTDs). For river blindness, a major NTD targeted for elimination, there is a long history of using vector control to suppress transmission, but traditional larvicide-based approaches are limited in their utility. One innovative and sustainable approach, "slash and clear", involves clearing vegetation from breeding areas, and recent field trials indicate that this technique very effectively reduces the biting density of Simulium damnosum s.s. In this study, we use a Bayesian data-driven mathematical modeling approach to investigate the potential impact of this intervention on human onchocerciasis infection. We developed a novel "slash and clear" model describing the effect of the intervention on seasonal black fly biting rates and coupled this with our population dynamics model of Onchocerca volvulus transmission. Our results indicate that supplementing annual drug treatments with "slash and clear" can significantly accelerate the achievement of onchocerciasis elimination. The efficacy of the intervention is not very sensitive to the timing of implementation, and the impact is meaningful even if vegetation is cleared only once per year. As such, this community-driven technique will represent an important option for achieving and sustaining O. volvulus elimination.

The positive influence the Onchocerciasis Elimination Program for the Americas has had on Africa programs.

A recent article "Is onchocerciasis elimination in Africa feasible by 2025: a perspective based on lessons learnt from the African control programmes" in Infectious Diseases of Poverty claimed that undue influence on African programs by concepts developed by the Onchocerciasis Elimination Program of the Americas (OEPA) is detrimental to stopping mass drug administration (MDA) in Africa. This claim is made despite a record year for MDA stoppage in four African countries of > 3.5 million treatments in 2018, far exceeding any past OEPA or African Program for Onchocerciasis Control (APOC) stop MDA success.

Comparison of Reported and Survey-Based Coverage in Onchocerciasis Programs over a Period of 8 Years in Cameroon and Uganda.

Mass drug administration (MDA) with ivermectin must reach a high treatment coverage (90% of the eligible population) if onchocerciasis is to be eliminated. Questions have been raised as to whether reported treatment figures reaching such high coverage are reliable. Sample surveys are proposed as the method of choice for "validating" reported coverage figures. The purpose of this study was to compare the district-level MDA coverage reported by programs with contemporaneous surveys of randomly selected respondents living in those same districts. Over an 8-year period, 19,219 households were selected using multistage random sampling; 38,433 adult male and female heads of those households were asked about their recent ivermectin MDA treatment experience. District coverage reports were considered "accurate" if they fell within the 95% CIs determined by the corresponding district's survey. Ninety-eight treatment rounds were evaluated over an 8-year period. Overall, the reported coverage of 96.5% (range: 68-100%) was significantly higher than the 92.5% surveyed coverage (range: 62.1-99.6%, 95% CI: 91.9-93.2%). However, only 20% of districts reported significantly higher coverage than surveys, 68% of district program reports were judged as accurate, and 12% of districts reported significantly lower coverage figures than their corresponding surveys. Eighty-eight percent of districts reported coverage ≥ 90% threshold for success, compared with 97% of surveys that included 90% in their 95% CIs. We conclude that when analyzed statistically at the district level, most surveys verified the reported coverage.

Author Correction: Substantiating freedom from parasitic infection by combining transmission model predictions with disease surveys.

The original version of this Article contained an error in the spelling of Emily Griswold, which was incorrectly given as Emily Grisworld. This error has now been corrected in both the PDF and HTML versions of the Article.

Substantiating freedom from parasitic infection by combining transmission model predictions with disease surveys.

Stopping interventions is a critical decision for parasite elimination programmes. Quantifying the probability that elimination has occurred due to interventions can be facilitated by combining infection status information from parasitological surveys with extinction thresholds predicted by parasite transmission models. Here we demonstrate how the integrated use of these two pieces of information derived from infection monitoring data can be used to develop an analytic framework for guiding the making of defensible decisions to stop interventions. We present a computational tool to perform these probability calculations and demonstrate its practical utility for supporting intervention cessation decisions by applying the framework to infection data from programmes aiming to eliminate onchocerciasis and lymphatic filariasis in Uganda and Nigeria, respectively. We highlight a possible method for validating the results in the field, and discuss further refinements and extensions required to deploy this predictive tool for guiding decision making by programme managers.

Operational Performance of the Onchocerca volvulus "OEPA" Ov16 ELISA Serological Assay in Mapping, Guiding Decisions to Stop Mass Drug Administration, and Posttreatment Surveillance Surveys.

Onchocerciasis is a neglected tropical disease targeted for elimination. The World Health Organization (WHO) has developed guidelines for the verification of onchocerciasis elimination that include entomological and epidemiological criteria. The latter require demonstrating with statistical confidence that the infection prevalence in children is less than 0.1%, necessitating an assay with a high degree of specificity. We present an analysis of the performance of the Onchocerciasis Elimination Program for the Americas (OEPA) version of the Ov16 enzyme-linked immunosorbant assay (ELISA) when used under operational conditions. In Africa and Latin America, the assay demonstrated 99.98% specificity in 69,888 children in 20 foci where transmission was believed to be interrupted. The assay produced a prevalence estimate equal to that of skin snip microscopy when applied in putatively hypo-endemic zones of Ethiopia. The OEPA Ov16 ELISA demonstrated the specificity required to be effectively deployed to verify transmission elimination under the WHO guidelines, while exhibiting a sensitivity equivalent to skin snip microscopy to identify hypo-endemic areas.

After 70 years of fighting an age-old scourge, onchocerciasis in Uganda, the end is in sight.

Onchocerciasis causes severe itching, serious skin disease and ocular damage leading to visual impairment or permanent blindness. It is associated with hanging groin, epilepsy, Nakalanga dwarfism and, most recently, nodding disease. This disease affected communities in 17 transmission foci in 37 districts of Uganda, where about 6.7 million people are once at risk. The efforts against onchocerciasis in Uganda commenced in the late 1940s, when vector control was launched using dichlorodiphenyltrichloroethane; by 1973, Simulium damnosum had been eliminated in the Victoria focus. Success outside of the Victoria focus was short-lived due to changes in government priorities and the political upheavals of the 1970s and 1980s. With the return of political stability, annual treatment with ivermectin through mass drug administration was launched in the early 1990s. Control of the disease has been successful, but there has been failure in interrupting transmission after more than 15 years. In 2007 Uganda launched a nationwide transmission elimination policy based on twice-per-year treatment and vector control/elimination, with a goal of eliminating river blindness nationwide by 2020. By 2017, 1 157 303 people from six foci had been freed from river blindness. This is the largest population ever declared free under World Health Organization elimination guidelines, providing evidence that elimination of river blindness in Africa is possible.

The role of national committees in eliminating onchocerciasis.

National onchocerciasis elimination committees (NOECs) serve to help ministries of health complete the pathway to successful verification of elimination of onchocerciasis (river blindness), as outlined in the 2016 World Health Organization guidelines. These guidelines, however, only take effect when the country believes it has reached a point that elimination can be demonstrated, and do not address the preceding milestones. Therefore, NOECs can be of great help with guiding and tailoring earlier planning, programming and assessments to empower national programs to aggressively move toward their countries' elimination goals. In this article, we provide suggestions for organizing NOECs and examples of four such committees that have successfully operated in Africa and the Americas.

The interruption of Onchocerca volvulus and Wuchereria bancrofti transmission by integrated chemotherapy in the Obongi focus, North Western Uganda.

INTERVENTION: Few studies have documented the interruption of onchocerciasis and Lymphatic Filariasis (LF) by integrated chemotherapy in Uganda. The study describes the interruption of transmission of the two diseases co-endemic in Obongi focus, north western Uganda. Base line data for Onchocerciasis and LF were collected in 1994 and 2006, respectively. Annual mass drug administration for onchocerciasis (Ivermectin) and Lymphatic Filariasis (Ivermectin + albendazole) was conducted for 20 and 6 years, respectively. Thereafter, assessments by skin snip, larval searches in rivers and human landing catches were performed. Children <10 years were screened for IgG4 antibodies using Ov16 ELISA technique in 2013. LF Pre-TAS and TAS1 were conducted in sentinel sites. ITN coverage and utilization for the implementation unit was also reported. INTERVENTION COVERAGE: Onchocerciasis treatment coverage was <80% but improved with the introduction of CDTI in 1999. While for LF, effective coverage of >65% was achieved in the six treatment rounds. Household ownership of ITN's and utilization was 96% and 72.4%., respectively. IMPACT: Parasitological examinations conducted for onchocerciasis among 807 adults and children, revealed a reduction in mf prevalence from 58% in 1994 to 0% in 2012. Entomological monitoring conducted at the two sites had no single Simulium damnosum fly caught. Serological analysis using Ov16 ELISA for onchocerciasis revealed that out of the 3,308 children <10 years old screened in 2013, only 3/3308 (0.091%) positive cases were detected. All Ov16 positive children were negative when tested for patent infection by skin snip PCR. A reduction in LF microfilaria prevalence from 2.5% (n = 13/522) in 2006 to 0.0% (n = 602) in 2014 was observed. LF TAS1 conducted in 2015 among 1,532 children 6-7 years, all were negative for antigens of W. bancrofti. CONCLUSION: The results concluded that interruption of onchocerciasis and LF has been achieved.

Molecular Identification of Onchocerca spp. Larvae in Simulium damnosum sensu lato Collected in Northern Uganda.

Previous studies have demonstrated that the presence of larvae of other filarial species in Simulium damnosum sensu lato can distort estimates of transmission potential for Onchocerca volvulus in West Africa. However, studies conducted in foci of onchocerciasis in West Central Uganda indicated that larvae other than O. volvulus were not common in vectors collected there. Recent data collected in Northern Uganda revealed a striking discordance between estimates of the prevalence of flies carrying O. volvulus infective larvae obtained from molecular pool screening and dissection methods. To resolve this discrepancy, sequences from three mitochondrially encoded genes were analyzed from the larvae collected by dissection. All larvae analyzed were Onchocerca ochengi v. Siisa, a parasite of cattle, or Onchocerca ramachandrini, a parasite of warthogs. These results suggest that nonhuman parasite larvae are common in vectors in Northern Uganda, underscoring the necessity for molecular identification methods to accurately estimate O. volvulus transmission.

The First Confirmed Elimination of an Onchocerciasis Focus in Africa: Abu Hamed, Sudan.

Mass treatment with ivermectin for onchocerciasis was stopped in 2012 in Abu Hamed, an isolated focus on the River Nile in northern Sudan. A 3-year posttreatment surveillance (PTS) ensued, at the end of which an evaluation was conducted in 2015 following the current World Health Organization guidelines for verification of onchocerciasis elimination. Vector black flies were collected from sentinel breeding sites and finger-prick bloodspots were collected from children ≤ 10 years of age resident in 35 communities within the focus. Polymerase chain reaction (PCR) screening of 19,191 flies from four sites for the O-150 parasite-specific marker found no flies carrying Onchocerca volvulus larvae (0%, 95% upper confidence limit [UCL] = 0.16), and serological testing of 5,266 children identified only one Ov16 seropositive child (0.019%, 95% UCL = 0.074); whose skin snips were negative when tested by O-150 PCR assay. These results indicate that for the first time in Africa, onchocerciasis elimination has been verified after a successful PTS in Abu Hamed.

The Imaramagambo Onchocerciasis Focus in Southwestern Uganda: Interruption of Transmission After Disappearance of the Vector Simulium neavei and Its Associated Freshwater Crabs.

It was not until early 1990s that, when the Imaramagambo focus of southwest Uganda was mapped, mass treatment with a single annual dose of ivermectin for onchocerciaisis control commenced. However, comprehensive investigations on its transmission were launched after a nationwide policy for onchocerciasis elimination in 2007. Entomological surveys throughout the focus from 2007 to 2015 have yielded few or no freshwater crabs (Potamonautes aloysiisabaudiae), which serve as the obligate phoretic host of the larvae and pupae of the vector Simulium neavei No S. neavei flies have been observed or collected since 2007. Skin snips (microscopy) from 294 individuals in 2008 were negative for skin microfilariae, and of the 462 persons analyzed by polymerase chain reaction skin snip poolscreen in 2009, only five (1.08%) persons were indicated as infected with onchocerciasis. All five of the positive persons were at least 40 years old. Serosurvey results showed negative exposure among 3,332 children in 2012 and 3,108 children in 2015. Both were within the upper bound of the 95% confidence interval of the prevalence estimate of 0.06%, which confirmed the elimination of onchocerciasis. Treatment coverage in Imaramagambo was generally poor, and transmission interruption of onchocerciasis could not be attributed solely to annual mass treatment with ivermectin. There was sufficient evidence to believe that the possible disappearance of the S. neavei flies, presumed to have been the main vector, may have hastened the demise of onchocerciasis in this focus.

Community-directed interventions are practical and effective in low-resource communities: experience of ivermectin treatment for onchocerciasis control in Cameroon and Uganda, 2004-2010.

BACKGROUND: The community-directed intervention (CDI) approach has improved treatment coverage in onchocerciasis-affected communities. However, there is still a lot to learn. This study assessed its performance and highlighted the lessons learnt so far. METHODS: Representative samples of households were selected from Cameroon and Uganda program areas through multi-stage random sampling. An adult male and female from every selected household were interviewed separately on their involvement in CDI activities every year between 2004 and 2010. Community health workers (CHWs) were interviewed and treatment records reviewed to determine whether 90% treatment coverage was attained within 2 weeks. Records related to training of CHWs and their supervisors were analyzed. RESULTS: Decision making decreased for community leaders and health workers, while it increased for community members. The proportion of CHWs attaining 90% treatment coverage within 2 weeks improved as their demand for monetary incentives, and number of persons they served, reduced. The number of CHWs supervised by a community supervisor remained low, but increased for the health workers. The cost of training a CHW and a community supervisor reduced to about US$1 and US$4.8, respectively. CONCLUSIONS: The CDI approach was effective, culturally appropriate and probably less costly in delivering health services in low-resource communities.

The Contributions of Onchocerciasis Control and Elimination Programs toward the Achievement of the Millennium Development Goals.

In 2000, 189 member states of the United Nations (UN) developed a plan for peace and development, which resulted in eight actionable goals known as the Millennium Development Goals (MDGs). Since their inception, the MDGs have been considered the international standard for measuring development progress and have provided a blueprint for global health policy and programming. However, emphasis upon the achievement of priority benchmarks around the "big three" diseases--namely HIV, tuberculosis (TB), and malaria--has influenced global health entities to disproportionately allocate resources. Meanwhile, several tropical diseases that almost exclusively impact the poorest of the poor continue to be neglected, despite the existence of cost-effective and feasible methods of control or elimination. One such Neglected Tropical Disease (NTD), onchocerciasis, more commonly known as river blindness, is a debilitating and stigmatizing disease primarily affecting individuals living in remote and impoverished areas. Onchocerciasis control is considered to be one of the most successful and cost-effective public health campaigns ever launched. In addition to improving the health and well-being of millions of individuals, these programs also lead to improvements in education, agricultural production, and economic development in affected communities. Perhaps most pertinent to the global health community, though, is the demonstrated effectiveness of facilitating community engagement by allowing communities considerable ownership with regard to drug delivery. This paper reviews the contributions that such concentrated efforts to control and eliminate onchocerciasis make to achieving select MDGs. The authors hope to draw the attention of public policymakers and global health funders to the importance of the struggle against onchocerciasis as a model for community-directed interventions to advance health and development, and to advocate for NTDs inclusion in the post 2015 agenda.